P768 Co-housing DSS treated mice with healthy mice results in faster recovery and normalization of the intestinal microbiota

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Background: The intestine is populated with myriads of bacteria, which form a complex ecosystem and have tremendous impact on our health. In inflammatory bowel disease (IBD), shifts in the microbial composition and a reduction in bacterial diversity have been described. There are attempts to therapeutically transfer the microbiota from healthy subjects to persons suffering from intestinal disease. While in case of Clostridium difficile infections, this approach proves to be very efficient, the therapeutic value of fecal microbial transfer (FMT) in IBD is still unclear. In mouse models of intestinal inflammation, the effect of FMT has been studied poorly and if so, germ-free or antibiotic-treated animals have been used – models that poorly reflect the situation in human IBD patients. Here, we addressed how transfer of microbiota from healthy to diseased mice affects recovery from acute colitis.

Methods: Acute colitis was induced in 12 week old C57B6 mice by administration of 2% DSS in the drinking water for 7 days. Mice with colitis were co-housed with healthy mice after removal of DSS. Due to coprophagy, this results in fast transfer of the microbiota between co-housed mice. To analyze changes in the microbial composition over time, stool samples were taken every second day and sequenced for the V4 hyper-variable region in the bacterial 16S DNA.

Results: As expected, DSS treatment resulted in severe weight loss, and even 7 days after withdraw of DSS (day 15), histology confirmed severe colitis. Intestinal inflammation was accompanied by an overall reduction of microbial diversity (decreased Shannon index, p<0.01), and a marked shift in the composition of the microbiota (increased abundance of Verrucomicrobia, Cyanobacteria and some families of Firmicutes [mainly Clostridiacea], although overall abundance of Firmicutes was decreased [p<0.01 for all]). However, on day 15, these changes were less pronounced, indicating a normalization of the microbiota composition upon recovery. DSS-treated mice which were co-housed with healthy littermates after colitis induction, showed faster recovery (earlier weight gain, reduced histological scores, reduced levels of the infiltration marker myeloperoxidase (MPO), less pronounced shortening of the colon, p<0.01 for all) and an earlier normalization of the microbiota composition.

Conclusions: Our results indicate that co-housing of DSS-treated mice with healthy mice results in transfer of the “healthy” microbiota to diseased mice, and promotes recovery from colitis. This indicates that introduction of a healthy microbiota might have beneficial effects during intestinal inflammation and opens the possibility to systematically study the effect of genetic alterations in donor and/or recipient on the efficacy of FMT.

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